The Late Endocytic Rab39a GTPase Regulates the Interaction Between Multivesicular Bodies and Chlamydial Inclusions

J Cell Sci. 2015 Aug 15;128(16):3068-81. doi: 10.1242/jcs.170092. Epub 2015 Jul 10.


Given their obligate intracellular lifestyle, Chlamydia trachomatis ensure that they have access to multiple host sources of essential lipids by interfering with vesicular transport. These bacteria hijack Rab6-, Rab11- and Rab14-controlled trafficking pathways to acquire sphingomyelin from the Golgi complex. Another important source of sphingolipids, phospholipids and cholesterol are multivesicular bodies (MVBs). Despite their participation in chlamydial inclusion development and bacterial replication, the molecular mechanisms mediating the interaction between MVBs and chlamydial inclusions remain unknown. In the present study, we demonstrate that Rab39a labels a subset of late endocytic vesicles - mainly MVBs - that move along microtubules. Moreover, Rab39a is actively recruited to chlamydial inclusions throughout the pathogen life cycle by a bacterial-driven process that depends on the Rab39a GTP- or GDP-binding state. Interestingly, Rab39a participates in the delivery of MVBs and host sphingolipids to maturing chlamydial inclusions, thereby promoting inclusion growth and bacterial development. Taken together, our findings indicate that Rab39a favours chlamydial replication and infectivity. This is the first report showing that a late endocytic Rab GTPase is involved in chlamydial infection development.

Keywords: Chlamydia trachomatis; Lipid transport; Multivesicular bodies; Pathogen–host-cell interaction; Rab; Rab39a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chlamydia trachomatis / metabolism*
  • Chlamydia trachomatis / pathogenicity
  • Cholesterol / metabolism
  • Golgi Apparatus / chemistry
  • HeLa Cells
  • Host-Pathogen Interactions / genetics
  • Humans
  • Multivesicular Bodies / metabolism*
  • Multivesicular Bodies / microbiology
  • Phospholipids / metabolism
  • Sphingolipids / metabolism*
  • Sphingomyelins / metabolism
  • Transport Vesicles / metabolism
  • rab GTP-Binding Proteins / metabolism*


  • Phospholipids
  • Sphingolipids
  • Sphingomyelins
  • Cholesterol
  • RAB39A protein, human
  • rab GTP-Binding Proteins